In studying immune surveillance mechanisms operative following human immunodeficiency virus (HIV-1) infection, we have concentrated on HIV-1 neutralizing antibodies which we first detected in 1985. In a limited survey, HIV-1-infected individuals with high geometric mean neutralizing antibody titers had lesser disease manifestations. Subsequently in pediatric AIDS cases, a relationship of neutralizing antibodies and a stable clinical state, as opposed to a poor one, was observed. In a retrospective investigation of HIV-1-sero-positive thalassemia patients, neutralizing antibodies also were associated with a better clinical outcome. Ongoing long-term prospective studies of HIV-1- infected individuals are aimed at elucidating any protective role of HIV-1 neutralizing antibodies. In related studies, the effect of HIV-1 envelope heterogeneity on the elicitation and function of neutralizing antibodies is being pursued. An HIV-1 variant virus was obtained by transmitting and propagating a cloned virus isolate in the presence of a neutralizing serum, indicating that type-specific neutralizing antibodies occur naturally. Whether such antibodies can cause immune selection of mutant viruses arising in vivo and influence disease progression remains to be determined. Genetic analysis of the variant has shown that a minor change was responsible for its loss of neutralizability. Further studies will pinpoint important epitopes. Other approaches for identification of neutralizing epitopes include use of a neutralizing monoclonal antibody to the viral gp120. In collaborative studies, the ability of various potential vaccine preparations to elicit high-titer, broadly reactive, neutralizing antibodies is being examined.